It is postulated that by suppressing JAK2 phosphorylation, NOT inhibits JAK2/STAT3 signaling, enhances intracellular ROS burst, and destabilizes VIM, Snail, β-catenin, or N-cadherin oncogene interaction with the stemness marker SOX2 or OCT4, thus suppressing tumorsphere formation and oncogenicity and consequently leading to HCC cell death as expressed by upregulated cleaved PARP levels. The gene discussed is POU5F1; the disease is hepatocellular carcinoma.